New benzimidazole-aldehyde hybrids as neuroprotectors with hypochlorite and superoxide radical-scavenging activity

Anastassova, Neda; Yancheva, Denitsa; Hristova-Avakumova, Nadya; Hadjimitova, Vera; Traykov, T.; Aluani, Denitsa; Tzankova, Virginia; Kondeva-Burdina, Magdalena

doi:10.1007/s43440-020-00077-3

Cited by 10 publications

(4 citation statements)

References 43 publications

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“…4 Furthermore, many benzimidazoles are screened for their potential anti-inflammatory, 5 antiviral 6 antiproliferative, and anthelmintic properties. 7 Likely, these compounds exhibited potent free radical scavenging properties as demonstrated in several reports, 8,9 which can be attributed to neuroprotection in Parkinson's, 10 Alzheimer's, 11 and other memory impairment models. 12,13 In this context, the beneficial effects of benzimidazole against multiple neurodegenerative's targets have been recently reviewed.…”

Section: Introductionmentioning

confidence: 71%

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

Ullah¹,

Kury²,

Althobaiti³

et al. 2022

JIR

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The study investigated the effect of newly synthesized benzimidazole derivatives against ethanol-induced neurodegeneration. According to evidence, ethanol consumption may cause a severe insult to the central nervous system (CNS), resulting in mental retardation, neuronal degeneration, and oxidative stress. Targeting neuroinflammation and oxidative stress may be a useful strategy for preventing ethanol-induced neurodegeneration. Methodology: Firstly, the newly synthesized compounds were subjected to molecular simulation and docking in order to predict ligand binding status. Later, for in vivo observations, adult male Sprague Dawley rats were used for studying behavioral and oxidative stress markers. ELIZA kits were used to analyse tumour necrosis factor-alpha (TNF-), nuclear factor-B (NF-B), interleukin (IL-18), and pyrin domain-containing protein 3 (NLRP3) expression, while Western blotting was used to measure IL-1 and Caspase-1 expression. Results: Our findings suggested that altered levels of antioxidant enzymes were associated with elevated levels of TNF-α, NF-B, IL-1, IL-18, Caspase-1, and NLRP3 in the ethanol-treated group. Furthermore, ethanol also caused memory impairment in rats, as measured by behavioural tests. Pretreatment using selected benzimidazole significantly increased the combat of the brain against ethanol-induced oxidative stress. The neuroprotective effects of benzimidazole derivatives were promoted by their free radical scavenging activity, augmentation of endogenous antioxidant proteins (GST, GSH), and amelioration of lipid peroxide (LPO) and other pro-inflammatory mediators. Molecular docking and molecular simulation studies further supported our hypothesis that the synthetic compounds Ca and Cb had an excellent binding affinity with proper bond formation with their targets (TNF-α and NLRP3). Conclusion: It is revealed that these benzimidazole derivatives can reduce ethanol-induced neuronal toxicity by regulating the expression of cytokines, antioxidant enzymes, and the inflammatory cascade.

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Section: Introductionmentioning

confidence: 71%

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

Ullah¹,

Kury²,

Althobaiti³

et al. 2022

JIR

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“…Similarly, compounds 502–503 demonstrated duel effects as anti-Alzheimer agents by beta amyloid cleavage enzyme-1 (BACE1) inhibition and neuroprotection ( Gurjar et al, 2020 ). In a 6-hydroxydopamine (6-OHDA)-induced oxidative stress in vitro model assay, compound 504 exerted neuroprotective action compared to melatonin, and reduced superoxide anion radical and hypochlorite level in a luminol-dependent chemiluminescent assay ( Anastassova et al, 2020 ). In another study, compound 505 displayed significant anti-neuroinflammatory property (IC 50 = 5.07 mM to prevent nitric oxide generation) and 65.7% hBACE1 inhibition.…”

Section: Biological Activitiesmentioning

confidence: 99%

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

et al. 2021

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Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

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“…A molecule capable of decreasing the amount of ROS can protect against cell damage and apoptosis [50]. Many researchers have suggested that the presence of conjugated double bonds throughout a molecule (as in the case of C40) can give intrinsic antioxidant properties through free radical scavenging [54,56,57].…”

Section: Ppar Researchmentioning

confidence: 99%

In Vivo and Ex Vivo Evaluation of 1,3-Thiazolidine-2,4-Dione Derivatives as Euglycemic Agents

Alemán-González-Duhart

Álvarez-Almazán

Valdés

et al. 2021

PPAR Research

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Thiazolidinediones (TZDs), used to treat type 2 diabetes mellitus, act as full agonists of the peroxisome proliferator-activated receptor gamma. Unfortunately, they produce adverse effects, including weight gain, hepatic toxicity, and heart failure. Our group previously reported the design, synthesis, in silico evaluation, and acute oral toxicity test of two TZD derivatives, compounds 40 (C40) and 81 (C81), characterized as category 5 and 4, respectively, under the Globally Harmonized System. The aim of this study was to determine whether C40, C81, and a new compound, C4, act as euglycemic and antioxidant agents in male Wistar rats with streptozotocin-induced diabetes. The animals were randomly divided into six groups ( n = 7 ): the control, those with diabetes and untreated, and those with diabetes and treated with pioglitazone, C40, C81, or C4 (daily for 21 days). At the end of the experiment, tissue samples were collected to quantify the level of glucose, insulin, triglycerides, total cholesterol, and liver enzymes, as well as enzymatic and nonenzymatic antioxidant activity. C4, without a hypoglycemic effect, displayed the best antioxidant activity. Whereas C81 could only attenuate the elevated level of blood glucose, C40 generated euglycemia by the end of the treatment. All compounds produced a significant decrease in triglycerides.

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New benzimidazole-aldehyde hybrids as neuroprotectors with hypochlorite and superoxide radical-scavenging activity

Cited by 10 publications

References 43 publications

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

In Vivo and Ex Vivo Evaluation of 1,3-Thiazolidine-2,4-Dione Derivatives as Euglycemic Agents

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